A group of experimental systems which allow the determination of quantitative endpoints in normal tissue and in tumors in the mouse will be used to search for methods which yield improved therapeutic ratios. Measurements of normal tissue damage to be applied include pulmonary, esophageal, renal, and brain lethality; intestinal crypt cell survival assays, mouse bone marrow CFU's survival assays, and skin reaction grading. Tumor endpoints to be applied include the use of the EMT6 mouse mammary tumor, the line 1 pulmonary tumor, the RIF sarcoma and the SQ1 squamous cell carcinoma. Tumors will be treated as solid tumors in the flank, in pulmonary micro- and macrocolonies, and the endpoints will be regrowth, tumor control, and cell survival measured in vitro after treatment in vivo. The radiation dose for damage to normal tissue and tumors with and without modifying agents, such as radiosensitizers, radioprotectors, hyperthermia, low dose rate, and high LET radiations, will be compared.